Abstract/Project summary Candidate Background My graduate and postdoctoral training have uniquely positioned me to combine comparative genomics and evolutionary biology with experimental molecular techniques, providing me with a powerful toolkit with which to answer questions in vector physiology. As a PhD student, I studied the evolutionary genomics of bacterial symbionts of insects in the Department of Ecology and Evolutionary Biology at The University of Arizona under the supervision of Prof. Nancy Moran. In my postdoctoral work in the labs of Prof. Michael Strand and Prof. Mark Brown in the Entomology Department at The University of Georgia, I developed a complementary set of skills in experimental molecular biology. Using my comparative genomics skills I identified a candidate receptor of ovary ecdysteroidogenic hormone, an essential regulator of mosquito reproduction. I then applied the molecular skills I learned as a postdoc to characterize the receptor and confirm it binds the hormone. I further used my skills in insect-microbe interactions to study the role of bacteria on larval mosquito development. I have been awarded an NIH F32 fellowship as a postdoctoral scientist and won several awards both at scientific meetings and my university for my research. Career Development Throughout my education, I have strived towards a career as an independent researcher. I have sought out career development opportunities and continue along a trajectory that will position me to successfully secure a position as an assistant professor at a research institution. This includes continued interaction with my advisors as well as outside scientists, presentation of my work at national and international scientific meetings, and publication of my research. This award will provide a strong foundation upon which I can build a career as a successful independent scientist. Immediate and long term career goals My immediate career goals are to complete my postdoctoral training and secure a tenure-track assistant professor position at a research institution. Having accomplished this, I will establish my research lab, including insect colonies and hiring personnel to assist with the research. Within one year of my position I anticipate completing Aim 1, and within two years I intend to have completed Aim 2 and published the research. Having established my lab and made significant progress in elucidating regulatory mechanisms of mosquito reproduction, I will complete and submit an R01 proposal to fully examine the role of the peptide hormone receptors in mosquito physiology. Within 5-6 years of my appointment, I expect to have successfully advanced to associate professor, trained several graduate and postdoctoral scientists, and established my lab as a major contributor to the field of vector biology. Proposed research Mosquitoes are the most significant arthropod vectors of human disease, and controlling their population is a major public health concern. One potential avenue for limiting mosquito populations is manipulating or disrupting their reproduction. Development of such strategies relies upon fully understanding the physiology of mosquito reproduction. Significant progress has been made in elucidating the biology of mosquito reproduction, particularly the role of peptide hormones. Several hormones are essential for successful egg production and regulate processes including blood meal digestion and egg maturation. These hormones transduce signals in target tissues via membrane-bound receptors, which are often attractive targets for pharmacological agonists/antagonists that disrupt the hormone's signaling cascade. Despite significant advances in our understanding of these peptide hormones and their receptors, a number of receptors remain so-called orphans, and have no known ligand and lack a characterized function. Using a comparative genomics framework, I identified three peptide hormone receptors in the genomes of several mosquito species whose ligands and functions are unknown, yet are highly expressed in mosquito ovaries during egg maturation. Phylogenetic analyses of the orphan receptors indicate that related receptors bind hormones with known roles in reproduction in other insects. Together, these data strongly suggest that the orphan peptide hormone receptors may be involved in mosquito reproduction. To further our understanding of these receptors I propose the following specific aims: 1. Determine the role of candidate receptors in mosquito reproduction through receptor knockdown and bioassays. 2. Identify the ligands of the receptors and characterize their binding dynamics in heterologous cell lines. Expected outcomes of this work include furthering our understanding of mosquito reproduction and its regulation. This research will impact the field of vector biology by identifying new avenues for potential control strategies aimed at limiting vector reproduction.